Attempts will be made to determine the precise metabolic mechanism which causes the cessation of galactocerebroside biosynthesis in globoid cell leukodystrophy, with the use of the canine GLD and CNS tissue explants. The experiments with dogs involve in vivo injection of isotopic galactose and sulfate, followed by the determination of their incorporation into cerebroside and sulfatide in the brain and kidney. Data are to be gathered on galactocerebrosidase activity on materials from family members of GLD patients, and the baseline will be established for heterozygote detection and prenatal diagnosis of the disease. The relationship between the nonspecific glycosidases measurable by artificial substrates and specific lipid glycosidases will be studied by preparing labelled specific lipid substrates, and by comparing the activity of the enzymes toward the lipid substrates and the artificial substrates. The use of cultured fibroblasts as the primary tool to study metabolic neurological disorders will be explored.